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Novel drug shuts down master protein key to lymphoma
Date:8/1/2013

mune system cells, not just B cells gone bad.

That finding suggested Bcl6 inhibiting drugs may have few side effects, says Dr. Melnick, who is also a hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The latest study was designed to understand exactly how Bcl6 promotes DLBCL.

Transcription factors are responsible for either inhibiting or promoting the expression of genes, and master regulatory transcription factors are like transcription factors on steroids: their actions regulate thousands of genes in different kinds of cells. Bcl6 can control the type of immune cell that develops in the bone marrow -- pushing them to become B cells, T cells, or macrophages -- and it has a primary role in the developmental phase of B cells, during which they generate specific antibodies against pathogens.

The researchers found that in order to help B cells produce antibodies against an infection, Bcl6 "builds a huge shopping mall-style complex" that sits on top of a stretch of the genome. By binding onto these genes, Bcl6 deactivates the DNA, stopping genes from producing RNA and proteins. "Bcl6 acts like a barcode reader. When it sees that barcode -- the DNA sequence -- it attaches there," Dr. Melnick.

Normally, the protein complex goes away after an immune reaction has been successfully mounted against the pathogen. But when it doesn't, and remains stuck to the genes, DLBCL can result. That's because Bcl6 is inhibiting genes that stop cells from dividing and that sense damage to the genome, Dr. Melnick says. "We now know the genes that Bcl6 is repressing and how that helps lymphoma develop and survive."

Bcl6 also has a second, independent function that Dr. Melnick says acts like a switch on railroad track that routes a train in one direction or another. One track is needed when antibodies are required for an immune response, while the other keeps B cells in a constant state of division.'/>"/>

Contact: John Rodgers
jdr2001@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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